Rat liver mitochondrial DNA has been isolated as a highly folded, compact structure that approximates the structure of the native packaged genome. This folded DNA can be isolated bound to the mitochondrial membrane-free form that has several tightly associated proteins. The proteins are being characterized with respect to their molecular weight and ionic properties. The nature of the bonds between the DNA and proteins in the complex and the role played by the proteins in the stabilization of the folded DNA structure are being investigated. The DNA-membrane complex will be characterized with respect to its macromolecular constituency, and the nature of the specific bonding of the DNA to the membrane will be studied. We will explore the possibility that a particular stage in the replication of mitochondrial DNA occurs concomitantly with the binding of the corresponding replicative intermediate to the membrane.